Safety of advanced therapies in pregnant women with inflammatory bowel disease: a systematic review and Meta-Analysis

BACKGROUND & AIMS: The expanding use of advanced IBD therapies creates an urgent need for pregnancy safety data. While anti-TNF safety is well-established, evidence for newer agents (vedolizumab, ustekinumab, and JAK inhibitors) remains limited. We aimed to quantify adverse pregnancy outcomes among women exposed to advanced therapies. METHODS: Random-effects models were used to calculate pooled prevalence estimates, with subgroup analyzes by therapeutic class. Restricted cubic spline meta-regression evaluated maternal age, disease activity, disease duration, phenotype, and third-trimester exposure as moderators. RESULTS: 67 observational studies with 17 441 pregnancies were included. Overall pooled prevalence rates were 8.2% (95% CI, 6.2-10.8) for early pregnancy loss, 8.9% (95% CI, 7.9-10.0) for preterm birth, 0.3% (95% CI, 0.2-0.6) for stillbirth, 6.6% (95% CI, 5.5-7.8) for low birth weight, 2.9% (95% CI, 2.2-3.9) for congenital malformations. JAK inhibitors and ustekinumab exposures were associated with higher pooled prevalence estimates of early pregnancy loss, while vedolizumab exposure was associated with higher estimates of preterm birth. Meta-regression identified disease duration, third-trimester exposure, maternal age, active disease, and Crohn's disease proportion as significant moderators of selected outcomes. CONCLUSION: Advanced IBD therapies demonstrate an overall favorable safety profile. Active disease, older maternal age, and longer disease duration were significant predictors of complications. Associations with third-trimester exposure do not support routine discontinuation, as this likely reflects underlying disease severity rather than treatment effect, reinforcing the priority of maintaining remission during pregnancy.